DETAILED ACTION
This office action is in response to applicant’s filing dated June 23, 2026.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Claims 19 and 21 – 26 are pending in the instant application. Receipt and consideration of Applicants' amended claim set and remarks/arguments filed on June 23, 2026 are acknowledged. Acknowledgement is made of Applicant's amendment of claims 19 and 21 – 25 and cancelation of claims 1 – 18, 20 and 27 - 28.
Claims 19 and 21 – 26 are under consideration in the instant office action.
Objections and/or Rejections and Response to Arguments
Applicants' arguments, filed on June 23, 2026, have been fully considered.
Acknowledgement is made of the Applicant’s amendment of claims 22 and 24 – 26 as described in Applicant’s arguments page 5, [0100] filed on June 23, 2026.
Accordingly, the rejection of claims 22 and 24 – 26 under 35 U.S.C. 112(a) for the lack of enablement is withdrawn.
Acknowledgement is made of the Applicant’s cancellation of claims 1, 9 and amendment of claims 19, 21 – 23 and 25. Amended claim 19 recites two compounds, which compounds would not be anticipated by applied art of Zhang et al., and claims 21 – 23 and 25 were amended to adjust dependency.
Accordingly, the rejection of claims 1, 9, 19, 21 – 23, 25 and 26 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Zhang et al is withdrawn.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated (Maintained Objections and/or Rejections) or newly applied (New Objections and/or Rejections, Necessitated by Amendment or New Objections and/or Rejections, NOT Necessitated by Amendment). They constitute the complete set presently being applied to the instant application.
Modified Objections and/or Rejections
Modifications Necessitated by Claim Amendment
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 19 and 21 – 26 are rejected under 35 U.S.C. 103 as being unpatentable over Adams et al (WO 2009/137391 A2, hereinafter Adams) in view of Zhang et al (WO 2014/194127 A1, cited in IDS, filed 02/10/2023).
Regarding claims 19 and 21, drawn to the compounds K5
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and K6
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or a pharmaceutically acceptable salt and a pharmaceutical composition thereof.
Adams teaches compounds of formula I-iii:
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where A is a phenyl or 5-6 membered heteroaryl (e.g. pyridinyl), such as compound of formula: I-vii:
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or I-iii-d:
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, where Q is C-R2 (R2 is F or Cl); R1 is halo, alkyl, haloalkyl, OR6 (R6 is H or alkyl); R3 is tert-butyl; R4 is -N(H)R8; R8 is -R5-NHC(O)2-R6 or -R5-NHC(O)-R5-OR6 ; R5 is C1-4 alkylene, linear or branched, such as methylene or ethylene, including-CH(CH3)- (pages 4 – 7, 34 and 38). The exemplary compounds taught by Adams are:
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(page 236, ex. 98),
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(page 335, ex. 290). Although Adams broadly teaches variable R8 structurally equivalent to the instantly claimed fragments
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and
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(see description of R8 above), Adams does not teach exact exemplary structures of said fragments identical to those of compounds K5 and K6.
However, Zhang teaches compounds of formula:
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(Ic-1a) (page 46, [0121]), such as compound P-2141
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(page 73, Table 1), where the corresponding fragment of exact structure is present
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(see the circled fragment). Compounds of Adams and Zhang act as agents inhibiting one or more Raf family kinases (e.g., B-Raf).
Thus, since Adams and Zhang teach compounds of the same utility and structure similar to instantly claimed compounds, it would be prima facie obvious to one of ordinary skill in the art before effective filing date of the claimed invention to combine teachings of prior art and make various structural analogs, by selecting and combining known structural elements to arrive at claimed compounds. The one of ordinary skills would be motivated to do so in search of an agent effectively inhibiting B-Raf kinase with improved efficacy and other desired properties with the reasonable expectation of success.
Regarding claims 22, 25 and 26, drawn to a method of treating a patient suffering from melanoma, lung cancer or colorectal cancer, comprising administering a therapeutically effective amount of a compound of formula K5 and K6 or salt thereof to the patient, or wherein the compound of formula K5 and K6 or salt thereof is a first active agent and is administered together with at least one additional active agent such as a MEK inhibitor, a CDK4/6 inhibitor or a PI3K inhibitor.
Adams teaches a method of treatment of neoplasm, such as cancer (colorectal cancer, lung cancer, skin cancer) where the method comprising administering to the patient a therapeutically effective amount of the compound of formula I-iii. (page 59, lines 29 – 35).
Zhang teach a method of treating a variety of cancers, such as human melanoma, colorectal and lung cancers comprising administering compound of formula (Ic-1a), e.g. compound P-2141 (page 128, [0223]). Zhang further teaches a method, where compound of formula (Ic-1a) or a pharmaceutically acceptable salt thereof is combined with another pharmacologically active compound, such as one or more therapeutic agents (e.g.: MEK inhibitors, Cdk4 inhibitors, PI3K inhibitors, etc.) (page 134 - 135, [0236]).
Regarding claim 23, drawn to a method of treating a patient suffering from a cancer susceptible to treatment with a RAF inhibitor, comprising administering a therapeutically effective amount of a compound of formula K5 and K6 or salt thereof to the patient. Adams teaches a method for treating neoplasm susceptible to mutation in BRaf (page 61, lines 13 – 15).
Zhang teaches a method of treating a variety of cancers, where the method includes selectively inhibiting a mutant RAF kinase, such as a mutant BRAF kinase (page 5, [0008]). Method taught by Zhang applies compounds of formula (Ic-1a) (e.g. compound P-2141), which act as RAF inhibitors, by selective inhibition of mutant BRAF protein kinases. Zhang demonstrates effectiveness of compounds on human cancer cell lines with BRAF V600E mutation (A375 melanoma, SKMEL3 melanoma, and COLO205 colon adenocarcinoma (page 126, [0217] and biochemical assays).
Regarding claim 24, drawn to a method of treating a patient suffering from a cancer, comprising:
(a) determining that a cell of the cancer contains a BRAFV600E mutation, and
(b) administering a therapeutically effective amount of a compound of formula K5 or K6 or salt thereof.
Adams teaches a method of treatment of cancer susceptible to mutation in BRAF, such as BRAFV600E, where the method comprises administering to the patient a therapeutically effective amount of the compound of formula I-iii (page 376, line 30).
Zhang teaches compound of formula Zhang further teaches a method of treating a cancer mediated by a BRAFV600E mutant, or a BRAFV600E/L505H mutant, wherein the method involves administering to the subject in need thereof an effective amount of one or more compound(s) of formula (Ic-1a) (e.g. compound P-2141) (pages 128 [0222] and 131, [0225]). The compounds, used in Zhang’s method act as RAF inhibitors, selectively inhibiting mutant BRAF protein kinases. Zhang demonstrates effectiveness of compounds on human cell lines with BRAF V600E mutation (A375 melanoma, SKMEL3 melanoma, and COLO205 colon adenocarcinoma (page 126, [0217] and biochemical assays).
Although Adams or Zhang do not explicitly teach the method where the method comprises determining that a cell of the cancer contains a BRAFV600E mutation, and then administering a therapeutically effective amount of a compound of formula K5 or K6, however it is within the level of knowledge of skilled artisan to recognize that if the method is adapted to treat cancer mediated by BRAFV600E mutation, then the mutation must be known, and thus, determined before starting said method of treatment.
Thus, it would be prima facie obvious to one of ordinary skill in the art before effective filing date of the claimed invention to apply teachings of prior art, which teaches a method of treating certain types of cancer mediated by BRAFV600E mutation with compounds selectively inhibiting mutant BRAF protein kinases, to achieve the claimed invention. A person of ordinary skill in the art would have been motivated to do so in search of an improved method of treating cancer mediated by certain mutations to selectively target these mutations with a reasonable expectation of success.
Therefore, taking all together, taught by prior art, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant argues:
- In view of claims cancellation, compounds of instant claims are not obvious variants of compounds taught by Zhang, as none of the compounds of Zhang has a phenyl or pyridyl group in at the position marked by a dotted line box on compounds K5 and K6 (see Applicant arguments page 8).
- Zhang discloses more than 180 other compounds along with IC50 V600E, ERK inhibitory activity and A375 inhibitory activity for more than 100 compounds. Biological data is not supplied for P-2141. Thus, there is no reason to select P-2141 from the many Zhang compounds for optimization.
Examiner’s response:
Applicant's arguments have been fully considered but they are not persuasive because: as set forth above, newly applied reference of Adams teaches compounds of similar structure with phenyl or pyridinyl ring in the position corresponding to instantly claimed compounds K5 and K6. Thus, combined prior art teaches compounds of the same utility, where all the structural elements equivalent to instantly claimed compounds.
Regarding the argument about absence of biological data for compound P-2141 is not persuasive because combined prior art teaches structurally analogous compounds of the same functionality. As states in MPEP 2143.I(B): “structural similarity can provide the necessary reason to modify prior art teachings. The Federal Circuit also addressed the kind of teaching that would be sufficient in the absence of an explicitly stated prior art-based motivation, explaining that an expectation of similar properties in light of the prior art can be sufficient, even without an explicit teaching that the compound will have a particular utility”.
Therefore, Applicant’s arguments are not persuasive and the rejection of claims 19 and 21 – 26 as obvious over teachings of Adams and Zhang is maintained.
Conclusion
Claims 19 and 21 – 26 are rejected. No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/E.V.V./ Examiner, Art Unit 1691
/SAVITHA M RAO/ Primary Examiner, Art Unit 1691
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